An estimated 6 million Americans suffer the often baffling symptoms of fibromyalgia or chronic fatigue syndrome. Patients with fibromyalgia, also referred to as fibromyalgia syndrome, FMS or fibrositis syndrome, report widespread musculoskeletal pain, chronic fatigue, and non-restorative sleep, and show specific regions of localized tenderness in the absence of demonstrable anatomic or biochemical pathology. Typically, they describe light and/or restless sleep. They awaken feeling unrefreshed with pain, stiffness, physical exhaustion, and lethargy. See, H. D. Moldofsky et al., J. Muscoloskel. Pain, 1, 49 (1993). In a series of studies, Moldofsky's group has shown that aspects of the patients' sleep pathology are related to their pain and mood symptoms. That is, patients with fibrositis syndrome show an alpha (7.5 to 11 Hz) electroencephalographic (EEG), non-rapid-eye-movement (NREM) sleep anomaly correlated with musculoskeletal pain and altered mood. Moldofsky has interpreted this alpha EEG NREM sleep anomaly to be an indicator of an arousal disorder within sleep associated with the subjective experience of non-restorative sleep. See H. D. Moldofsky et al., Psychosom. Med., 37, 341 (1975).
Fibromyalgia patients frequently report symptoms similar to those of patients with post-infectious neuromyasthenia, also referred to as chronic fatigue syndrome (CFS). Chronic fatigue syndrome, or CFS, is a debilitating disorder characterized by profound tiredness or fatigue. Patients with CFS may become exhausted with only light physical exertion. They often must function at a level of activity substantially lower than their capacity before the onset of illness. In addition to these key defining characteristics, patients generally report various nonspecific symptoms, including weakness, muscle aches and pains, excessive sleep, malaise, fever, sore throat, tender lymph nodes, impaired memory and/or mental concentration, insomnia, and depression. CFS can persist for years. Compared with fibromyalgia patients, chronic fatigue patients have similarly disordered sleep, localized tenderness, and complaints of diffuse pain and fatigue.
The presence of considerable symptom overlap in FMS and chronic fatigue syndrome has led to speculation that they may represent different facets of the same underlying, as yet unknown disease process (D. L. Goldenberg, J. Musculoskel. Med., 7, 19 (1990); D. L. Goldenberg, Arth. Rheum., 33, 1132 (1990); M. B. Yunus, J. Rheumatol., 16 (S19), 62 (1989)). Although no specific inheritance pattern has been identified, an increased incidence in relatives of affected patients has been noted (M. J. Pellegrino et al., Arch. Phys. Med. Rehab., 70, 61 (1989)). Development of the syndrome may require a predisposing factor, possibly inherited, as well as a precipitating factor, perhaps something disturbing sleep.
Amitriptyline can be an effective medication for FMS but it also has frequent side effects when used in doses sufficient to keep FMS symptoms well controlled. Particularly bothersome are weight gain, dry mouth, and daytime cognitive impairment. See, D. L. Goldenberg et al., Arth. Rheum., 29, 1371 (1986). Diphenhydramine and trazodorie are in common use because they seem effective and have less side effects, but have not been proven to work in controlled, blinded trials. It is often necessary to try several different medications in succession before finding one that works well with acceptable side effects. Some tolerance develops to the sedative effect of many of these medications, necessitating one or two dose increases after an initial good response to maintain it. There is no pharmacological therapy recognized as effective for CFS.
Therefore, a need exists for an effective drug-based treatment of FMS and/or chronic fatigue syndrome that does not exhibit undue side effects.